Journal Article

A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex

Vaishnav, Eeshit Dhaval, Osteen, Julia K., Ngai, John, Macosko, Evan Z., Kharchenko, Peter V., Huang, Z. Josh, Dee, Nick, Bartlett, Anna, Risso, Davide, Crow, Megan, Vanderburg, Charles R., Bertagnolli, Darren, Crichton, Kirsten, Adkins, Ricky S., Tasic, Bosiljka, Creasy, Heather, Pham, Thanh, van Velthoven, Cindy, Fong, Olivia, Street, Kelly, Aldridge, Andrew I., Hu, Qiwen, Xie, Fangming, Colantuoni, Carlo, Li, Yang Eric, Kancherla, Jayaram, Wang, Xinxin, Ren, Bing, Giglio, Michelle, Nery, Joseph R., Regev, Aviv, Hawrylycz, Mike, Ntranos, Vasilis, Ecker, Joseph R., Zeng, Hongkui, Nadaf, Naeem M., Tieu, Michael, Kroll, Matthew, McMillen, Delissa, Welch, Joshua D., Lathia, Kanan, Pinto-Duarte, Antonio, Fischer, Stephan, Smith, Kimberly, Behrens, M. Margarita, Lucero, Jacinta D., Hertzano, Ronna, Svensson, Valentine, Doyle, Wayne I., Dougherty, Elizabeth L., Hou, Xiaomeng, Purdom, Elizabeth, Bravo, Héctor Corrada, Orvis, Joshua, Liu, Hanqing, Casper, Tamara, Tung, Herman, White, Owen R., Rivkin, Angeline C., Sulc, Josef, Dudoit, Sandrine, Crabtree, Jonathan, Ament, Seth A., Poirion, Olivier, Herb, Brian R., Preissl

2021

Overview

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain 1 – 3 . With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas—containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities—is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions 4 . We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis. The authors describe an integrated atlas of the diverse cell types in the mouse primary motor cortex.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 38/91 / 45/22 / 631/208/177 / 631/208/191/2018 / 631/378/2632/1663 / 631/378/340 / 631/378/87 / 64/60 / Animals / Atlases as Topic / Biological effects / Computational neuroscience / Cortex (motor) / Datasets / Datasets as Topic / DNA methylation / Epigenesis, Genetic / Epigenomics / Female / Functional analysis / Gene expression / Gene Expression Profiling / Humanities and Social Sciences / Locomotion / Male / Mice / Motor Cortex - anatomy & histology / Motor Cortex - cytology / multidisciplinary / Neurons - classification / Neurons - cytology / Neurons - metabolism / Organ Specificity / Pyramidal cells / Regulatory sequences / Reproducibility of Results / Science / Science (multidisciplinary) / Single-Cell Analysis / Statistical methods / Taxonomy / Transcriptome / Transcriptomes